title: Prostaglandin-independent stimulation of bone resorption in mouse calvariae and in isolated rat osteoclasts by thyroid hormones (T4, and T3).
abstract: The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), were found to enhance both neonatal mouse calvarial bone resorption and pit formation on bovine slices by isolated rat osteoclasts. Dosage-dependent release of 45Ca from mouse calvarial bones was observed after 120 hr of culture with 10(-6)-10(-8) MT4 and 10(-6)-10(-10) M T3. Maximum treatment/control ratios of 45Ca release were recorded for 10(-7) M T4 and 10(-8) MT3. Inhibition of 45Ca release stimulated by 10(-8) M T3 was observed in the presence of 30 nM salmon calcitonin at 48 hr and 120 hr of culture with no indication of "escape" by T3-treated bones. In contrast, stimulation of 45Ca release from mouse calvarial bones by 10(-7) MT4 and 10(-8) MT3 was not inhibited by 10(-6) M indomethacin. Formation of PGE2 and PGI2 (evaluated by measuring 6-keto-PGF1alpha) by mouse calvariae was also not increased by 10(-8) MT3 after 120 hr of culture. Furthermore, no increases in cAMP formation were observed in calvarial bone cultures after either 10 min or 24 hr of exposure to 10(-8) MT3. However, significant inhibition of 45Ca release stimulated by 10(-8) M T3 was found at 120 hr in the presence of 10(-3) M hydroxyurea. When isolated rat osteoclasts were cultured in the presence of 10(-7) MT3, a 1.4-fold stimulation of pit number was observed. Pit formation was not affected by addition of 10(-6) M indomethacin to either the control or T3-treated cultures. These data suggest that the stimulation of bone resorption in neonatal mouse calvariae and activation of isolated rat osteoclasts by the thyroid hormones is not related to either prostaglandin or cAMP formation. In mouse calvariae, the effect on bone resorption of the thyroid hormones is dependent on increased cellular replication, perhaps of osteoclast precursors, or other bone cells involved in the resorptive process.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Conaway
authors.forename: M
authors.initials: M
authors.lastname: Ransjö
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D001862:Bone Resorption; D002116:Calcitonin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006918:Hydroxyurea / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects*; D010281:Parathyroid Hormone / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D012886:Skull / Q000187:drug effects; D013974:Thyroxine / Q000494:pharmacology*; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D010710:Phosphates; D011453:Prostaglandins; D014284:Triiodothyronine; D015121:6-Ketoprostaglandin F1 alpha; D002116:Calcitonin; D000242:Cyclic AMP; D000118:Acetylglucosaminidase; D015232:Dinoprostone; D013974:Thyroxine; D002118:Calcium; D006918:Hydroxyurea; D007213:Indomethacin